An efficient protocol for the synthesis of pyridines and hydroquinolones using IRMOF-3/GO/CuFe2O4 composite as a magnetically separable heterogeneous catalyst

This study reports a facile and cost-effective technique for preparing magnetic copper ferrite nanoparticles supported on IRMOF-3/GO [IRMOF-3/GO/CuFe2O4]. The synthesized IRMOF-3/GO/CuFe2O4 was characterized with IR, SEM, TGA, XRD, BET, EDX, VSM, and elemental mapping. The prepared catalyst revealed higher catalytic behavior in synthesizing heterocyclic compounds through a one-pot reaction between various aromatic aldehydes, diverse primary amines, malononitrile, and dimedone under ultrasound irradiations. Among the notable features of this technique are higher efficiency, easy recovery from the reaction mixture, removal of a heterogeneous catalyst, and uncomplicated route. In this catalytic system, the activity level was almost constant after various stages of reuse and recovery.


Preparation of IRMOF-3/CuFe 2 O 4 nanocomposite.
A mixture of CuFe 2 O 4 (0.05 g), Zn (NO 3 ) 2· 6H 2 O (0.066 g) and NH 2 -BDC (0.016 g) was dissolved in DMF (10 mL) under vigorous stirring. Next, the solution was transferred to an autoclave and heated at 120 °C for 10 h. The precipitate was separated after cooling, by a simple filtration. The obtained crystals were then soaked in 20 mL of DMF at 80 °C for 12 h. Lastly, the obtained IRMOF-3/CuFe 2 O 4 was dried for 24 h at 40 °C 29 .
The scanned original spectral data of new compounds are provided in Supporting Information.

Results and discussion
IRMOF-3/GO/CuFe 2 O 4 was successfully synthesized as mentioned in our previous study 31 . The structure of this catalyst was determined using EDX/Mapping, IR, and TGA analysis (See Supplementary  The microscopic morphology of the products was visualized by scanning electron microscopy (SEM). This analysis showed that CuFe 2 O 4 is composed of relatively uniform quasispherical particles (Fig. 2a) 32 . SEM images of IRMOF-3 showed that this structure has a crystalline and rod shape, per previous reports ( Fig. 2b) 33 . SEM image of the GO shows the particles of GO look very dense with the layers stacked together due to dispersive forces and strong specific interactions between the surface groups on the graphene-like layers ( Fig. 2c) 34  Nitrogen adsorption/desorption isotherms were used to study the specific surface area and pore volume distribution of nanostructures including CuFe 2 O 4 , GO, IRMOF-3, and IRMOF-3/GO/CuFe 2 O 4 by the Brunauer-Emmett-Teller (BET) approach (Fig. 4). The CuFe 2 O 4 represented a BET surface area, total pore volume, and the average pore diameter of 34.65 m 2 g −1 , 0.138 cm 3 g −1 , and 1.17 nm respectively. In comparison, these analyses for GO, IRMOF-3 and IRMOF-3/GO/CuFe 2 O 4 gave values of 48.51 m 2 g −1 , 0.182 cm 3 g −1 , and 1.24 nm, 884.82 m 2 g −1 , 0.887 cm 3 g −1 , and 1.42 nm, and 456.29 m 2 g −1 , 0.435 cm 3 g −1 and, 1.65 nm, respectively ( Fig. 4 and Table 1). The adsorption-desorption isotherm of all the four samples exhibits a reversible type-II adsorption isotherm, indicating the presence of micro-and macro-pores 39 . The decreasing BET surface area and total pore volume can be attributed to incorporating of IRMOF-3/CuFe 2 O 4 groups inside the pure GO. However, the open cavities and high surface areas were retained, which benefited the free dispersal of the reactant and product.
The so-called VSM analysis was further conducted to investigate the magnetic behavior of the IRMOF-3/ CuFe 2 O 4 , and IRMOF-3/GO/CuFe 2 O 4 nanocomposite, with the outcomes presented in Fig. 5. According to the results, the value of magnetic saturation was measured at 67.45, and 38.45 emu/g for the IRMOF-3/CuFe 2 O 4 and IRMOF-3/GO/CuFe 2 O 4 nanocomposite, respectively 40 .
The performance of the prepared IRMOF-3/GO/CuFe 2 O 4 nanocomposite was evaluated using the catalyst in the preparation of 2-amino-4-aryl-6-substituted pyridine-3,5-dicarbonitrile and hydroquinoline-3-carbonitrile     www.nature.com/scientificreports/ Table 2 shows no product was achieved without any solvent under ultrasonic irradiation. Furthermore, it was concluded that the presence of ethanol as solvent provided the best outcome considering reaction time and yield of the corresponding product. Subsequently, the preparation of hexahydroquinoline-3-carbonitrile (6b) was also examined using different polar and nonpolar solvents ( Table 2, entries 23-28). As indicated in this Table 2, using EtOH as solvent provided the best reaction conditions ( Table 2, entries 20 and 26).
In the next stage, it was decided to assess the optimum amount of the nanocatalyst for preparing of 4e and 6b. Different amounts of the catalyst were used for preparing 2-amino-4-(4-bromophenyl)-6-(p-tolylamino)pyridine-3,5-dicarbonitrile and 2-amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-1-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (Table 3). The model was run using various amounts of the catalyst from 0.001 to 0.007 g. Eventually, the optimal amounts were found to be 0.003 and 0.005 g for compounds 4e and 6p, respectively. Some aromatic aldehydes and amines were used to investigate the catalytic efficiency and performance of the IRMOF-3/GO/CuFe 2 O 4 on synthesizing various pyridine and hydroquinoline derivatives under optimized reaction conditions. After conducting some experiments, we obtained some 2-amino-4-aryl-6-substituted-pyridine-3,5-dicarbonitriles and hydroquinolone-3-carbonitriles in good to excellent yields within short reaction times. As illustrated in Table 4, different aldehydes and anilines with various substituents could participate in the multi-component synthesis of corresponding heterocyclic compounds. However, as indicated, benzaldehydes with electron-withdrawing groups reacted faster than electron-donating ones. Moreover, the aromatic amines having electron-releasing groups reacted faster than anilines containing electron-withdrawing groups. According to the mechanism pathway, the first step of the mechanism is the Knoevenagel condensation between malononitrile and aromatic aldehyde. Obliviously, the presence of electron-withdrawing groups on the benzaldehydes leads to a faster reaction due to more electrophilicity of the carbon group of the carbonyl 41,42 . While using IRMOF-3/GO/CuFe 2 O 4 as a catalyst serves as a Lewis acid catalyst and increases the electrophilicity of the carbonyl groups of aldehydes. The synergic effects of both electron-withdrawing groups and Lewis acidity of IRMOF-3/GO/CuFe 2 O 4 increase the reaction rate. Nevertheless, against the electron-withdrawing groups, the existence of electron-donating groups lowers the speed of the reaction, because of a slower nucleophilic attack on carbonyl groups of aldehydes.
The catalyst efficiency and usability for synthesizing 2-amino-4-aryl-6-substituted pyridine-3,5-dicarbonitrile and hydroquinoline-3-carbonitrile derivatives were compared with those of some previously reported catalysts. As presented in Table 5, IRMOF-3/GO/CuFe 2 O 4 is better than previously reported catalysts in saving time, and energy, and excellent yields of the products ( Table 5).

Reuse of catalyst. In this research, the reusability of IRMOF-3/GO/CuFe 2 O 4 composite was investigated
for the three-component reaction of 4-bromobenzaldehyde, p-toluidine, and malononitrile (compound 4e). Upon completion of the reaction, the IRMOF-3/GO/CuFe 2 O 4 nanostructure was separated using a centrifuge instrument and washed with dichloromethane. The obtained recovered catalyst was dried at 40 °C for 24 h. As indicated in Fig. 6, the recovered catalyst could be used 7 times. Furthermore, the XRD technique was used to demonstrate the efficiency and consistency of the rescue IRMOF-3/GO/CuFe 2 O 4 after seven runs uses. As  www.nature.com/scientificreports/  www.nature.com/scientificreports/ indicated, there is no considerable differences between X-ray diffraction of the fresh IRMOF-3/GO/CuFe 2 O 4 and the recovered catalyst, confirming the good stability of the prepared nanocatalyst after 7 runs (Fig. 7). Figure 8 shows a reasonable mechanism for synthesizing pyridine derivatives (4a-4r) catalyzed by IRMOF-3/ GO/CuFe 2 O 4 , This result is, supported by previous studies 41   www.nature.com/scientificreports/ Finally, 2-amino-6-alkylamino-3,5-dicyanopyridines 4 was prepared by aromatization of intermediate III.
Additionally, the catalytic behavior of IRMOF-3/GO/CuFe 2 O 4 on the quinoline synthesis was identical to the described mechanism for synthesizing pyridine derivatives.

Conclusion
The present work aimed to present a convenient and facile technique to prepare magnetic copper ferrite nanoparticles supported on IRMOF-3/GO. This magnetic heterogeneous and reusable nano catalyst to prepare heterocyclic compounds via the reactions between of various aromatic aldehydes, malononitrile, diverse primary amines and dimedone under ultrasound irradiations. The methods for characterizing the IRMOF-3/GO/CuFe 2 O 4 were SEM, BET, FT-IR, XRD, TGA, and EDX. It was indicated that this catalyst is effective for synthesis of pyridines and quinoline derivatives. Moreover, this technique has good benefits like eco-friendly, higher performance and a very convenient working technique.